Heat shock protein 90α inhibitor, PU-H71 in combination with DHEA promoting apoptosis in triple-negative breast cancer cell line MDA-MB-231

Hadeer Soudan; Hesham Saeed; Maha Eldemellawy; Manal Shalaby; Mostafa Hassan; Mohamed Elkewedi; Nefertiti El-Nikhely

doi:10.18388/abp.2020_5418

Hadeer Soudan Department of Biotechnology, Institute of Graduate Studies and Research, Alexandria University, Alexandria, Egypt
Hesham Saeed Department of Biotechnology, Institute of Graduate Studies and Research, Alexandria University, Alexandria, Egypt https://orcid.org/0000-0001-6600-1338
Maha Eldemellawy Genetic Engineering and Biotechnology Research Institute (GEBRI), City for Scientific Research and Technology Applications, New Borg Al-ArabCity, Alexandria, Egypt; Center of Excellence for Drug Preclinical Studies, City for Scientific Research and Technology Applications, New Borg Al-Arab City, Alexandria, Egypt
Manal Shalaby Genetic Engineering and Biotechnology Research Institute (GEBRI), City for Scientific Research and Technology Applications, New Borg Al-ArabCity, Alexandria, Egypt https://orcid.org/0000-0002-9617-4886
Mostafa Hassan Department of Environmental Studies, Institute of Graduate Studies and Research, Alexandria University, Alexandria, Egypt https://orcid.org/0000-0002-4201-5409
Mohamed Elkewedi Department ofMedical Laboratory Technology, Faculty of Applied Health Sciences Technology, Pharos University in Alexandria, Alexandria, Egypt
Nefertiti El-Nikhely Department of Biotechnology, Institute of Graduate Studies and Research, Alexandria University, Alexandria, Egypt

DOI: https://doi.org/10.18388/abp.2020_5418

Abstract

Due to the lack of markers (ER, PR, and HER-2/Neu) for the molecular-targeted therapies triple-negative breast cancer (TNBC) is more challenging than other subtypes of breast cancer. Moreover, the conventional chemotherapeutic agents are still the mainstay of most therapeutic protocols and eventually turn into a refractory drug-resistance , hence, more efficient therapeutic regimens are urgently required. The present study aimed to elucidate the effects of PU-H71 combined with DHEA on triple-negative breast cancer cell line MDA-MB-231 and to assess the synergy using the Chou-Talalay method. The combined therapy controlled the expression of an array of antioxidants and metabolizing enzymes, leading to the induction of oxidative stress which in turn induced apoptotic cell death. Our results indicated that the combined treatment with PU-H71 and DHEA exerts a synergistic anti-tumor effect on MDA-MB-231 triple-negative breast cancer cell line.